Efficacy of long-term growth hormone therapy in short non-growth hormone-deficient children

2017 ◽  
Vol 30 (2) ◽  
Author(s):  
Lucia Schena ◽  
Cristina Meazza ◽  
Sara Pagani ◽  
Valeria Paganelli ◽  
Elena Bozzola ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Final Height ◽  
Standard Deviation Score ◽  
Bone Age ◽  
Gh Treatment ◽  
Short Children ◽  
Igf I ◽  
Height Gain ◽  
The Cost

AbstractBackground:In recent years, several studies have been published showing different responses to growth hormone (GH) treatment in idiopathic short stature children. The aim of the present study was to investigate whether non-growth-hormone-deficient (non-GHD) short children could benefit from long-term GH treatment as GHD patients.Methods:We enrolled 22 prepubertal children and 22 age- and sex-matched GHD patients, with comparable height, body mass index (BMI), bone age, and insulin-like growth factor 1 (IGF-I) circulating levels. The patients were treated with recombinant human GH (rhGH) and followed until they reach adult height.Results:During GH treatment, the two groups grew in parallel, reaching the same final height-standard deviation score (SDS) and the same height gain. On the contrary, we found significantly lower IGF-I serum concentrations in non-GHD patients than in GHD ones, at the end of therapy (p=0.0055).Conclusions:In our study, the response to GH treatment in short non-GHD patients proved to be similar to that in GHD ones. However, a careful selection of short non-GHD children to be treated with GH would better justify the cost of long-term GH therapy.

Acromesomelic Dysplasia, Type Maroteaux: Impact of Long-Term (8 Years) High-Dose Growth Hormone Treatment on Growth Velocity and Final Height in 2 Siblings

2020 ◽  
Vol 93 (5) ◽  
pp. 335-342
Author(s):  
Ved Bhushan Arya ◽  
Meena Raj ◽  
Maha Younes ◽  
Simon Chapman ◽  
Melita Irving ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Serum Insulin ◽  
Final Height ◽  
Hormone Treatment ◽  
High Dose ◽  
Childhood And Adolescence ◽  
Loss Of Function ◽  
Gh Treatment ◽  
Height Gain

<b><i>Introduction:</i></b> Acromesomelic dysplasia, type Maroteaux (AMDM) is a rare autosomal recessive skeletal dysplasia, characterized by severe dwarfism and disproportionate limb shortening. It results from loss-of-function <i>NPR2</i> mutations affecting the C-type natriuretic peptide receptor. Resistance to growth hormone (GH) action has previously been suggested. We describe outcomes of 2 siblings with AMDM after prolonged high-dose GH treatment. <b><i>Patients/Methods:</i></b> Two siblings (Pt-A and Pt-B; consanguineous parents) presented in early childhood with severe disproportionate short stature and radiological features of AMDM. Subsequent genetic testing identified a novel homozygous <i>NPR2</i> mutation. GH provocation testing showed relatively high GH levels. Serum insulin-like growth factor 1 (IGF-1) was ∼2 SD below age/sex-specific mean. High-dose GH (0.075 mg/kg/day) was started. Pre-GH height velocities were 3.7 (Pt-A) and 4.5 (Pt-B) cm/year. GH dose was adjusted to sustain serum IGF-1 towards +3 SDS for age/sex. Annualized height velocities for first 3 years on GH were 7.0, 5.4, and 4.7 cm/year for patient A and 9.4, 8.0, and 5.9 cm/year for patient B. Height gain during puberty was 10.6 (Pt-A) and 5.9 (Pt-B) cm. Final heights after 8.5 years of GH treatment were 130.5 cm (−6.57 SDS, Pt-A) and 134 cm (−4.58 SDS, Pt-B). <b><i>Conclusions:</i></b> To the best of our knowledge, this is the first report of final height in patients with AMDM after long-term GH treatment. Our results confirm the finding of relative GH resistance in AMDM, which when overcome with high-dose GH treatment resulted in improved height SDS during childhood and adolescence and associated quality of life. The final height of our patients was significantly higher than average reported final height (120 cm) of AMDM patients.

scholarly journals Long-Term Effectiveness and Safety of Childhood Growth Hormone Treatment in Noonan Syndrome

2020 ◽  
Vol 93 (6) ◽  
pp. 380-395
Author(s):  
Tilman R. Rohrer ◽  
Jennifer Abuzzahab ◽  
Philippe Backeljauw ◽  
Anna Camilla Birkegård ◽  
Joanne Blair ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Adverse Events ◽  
Noonan Syndrome ◽  
Standard Deviation Score ◽  
Hormone Treatment ◽  
Gh Treatment ◽  
Serious Adverse Events ◽  
Height Gain ◽  
The Mean

<b><i>Introduction:</i></b> Few data exist on long-term growth hormone (GH) treatment in patients with Noonan syndrome (NS). <b><i>Objective:</i></b> To evaluate the effectiveness and safety of GH treatment in NS in clinical practice. <b><i>Methods:</i></b> Height gain, near-adult height (NAH), and safety were assessed in 2 complementary non-interventional studies: NordiNet® IOS and ANSWER. The safety analysis included 412 patients, and the effectiveness analysis included 84 GH-treated patients (male, <i>n</i> = 67) with ≥4 years’ height standard deviation score (HSDS) data. HSDS was determined using national reference (NR) and NS-specific (NSS) data. <b><i>Results:</i></b> The mean (SD) baseline age was 8.38 (3.57) years; HSDS, −2.76 (1.03); GH dose, 41.6 (11.1) µg/kg/day. The mean (SD) HSDS increase from baseline (ΔHSDS) was 0.49 (0.37) (first year), 0.79 (0.58) (second year), and 1.01 (0.60) (third year) (NR). The mean (SD) HSDS at year 3 was −1.66 (1.00) (NR; 1.06 [1.12] [NSS]). Twenty-four patients achieved NAH. The mean (SD) NAH SDS (NR) was −1.51 (0.60) (154.90 [3.21] cm) in females and −1.79 (1.09) (165.61 [7.19] cm) in males; 70.8% (17/24) had NAH SDS ≥ −2. Adverse drug reactions and GH-unrelated serious adverse events (<i>n</i> = 34) were reported in 22/412 (5.3%) patients. Four neoplasms and 3 cases of scoliosis were reported; no cardiovascular adverse events occurred. <b><i>Conclusions:</i></b> GH-treated children with NS achieved substantial height gain during the first 3 years of follow-up. Overall, 24 patients achieved NAH, with 70.8% having NAH SDS ≥ –2. There was no evidence to support a higher prevalence of neoplasm, or cardiac or other comorbidities.

scholarly journals Growth Hormone Therapy Benefits Pituitary Stalk Interruption Syndrome Patients with Short Stature: A Retrospective Study of 75 Han Chinese

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Cheng-Zhi Wang ◽  
Ling-Ling Guo ◽  
Bai-Yu Han ◽  
An-Ping Wang ◽  
Hong-Yan Liu ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Final Height ◽  
Bone Age ◽  
Pituitary Stalk ◽  
Gh Therapy ◽  
Gh Treatment ◽  
Significant Difference ◽  
Height Gain ◽  
The Impact

Objective. We aim to investigate the long-term benefits of growth hormone (GH) therapy in short stature adolescents and adults with pituitary stalk interruption syndrome (PSIS), which would be beneficial for future clinical applications.Design and Methods. In this study, initial height, final height, total height gain, and GH treatment history were retrospectively investigated in 75 Chinese PSIS patients. We compared height gain between the GH treated cohort and untreated cohort and explored the impact of different GH therapy duration on height gain.Results. For GH treated patients, their final height (SDS) increased from-1.99±1.91(−6.93~2.80) at bone age (BA) of 11.2 (5.0~17.0) years to-1.47±1.64(−7.82~1.05) at BA of 16.6 (8.0~18.0) years (P=0.016). And GH treated patients had more height gain than the untreated patients (P<0.05). There was a significant difference between the different GH therapy duration groups (P=0.001): GH 0 versus GH 3,P=0.000; GH 1 versus GH 3,P=0.028; GH 2 versus GH 3,P=0.044.Conclusion. Adult Chinese PSIS patients with short stature benefited the most from at least 12 months of GH therapy. Although patient diagnosis age was lagged behind in the developing countries, GH treatment was still effective for them and resulted in a higher final height and more height gain.

Height Increment and Laboratory Profile of Boys Treated With Aromatase Inhibitors With or Without Growth Hormone

2017 ◽  
Vol 49 (10) ◽  
pp. 778-785 ◽  
Author(s):  
Ludmila Pedrosa ◽  
Joice de Oliveira ◽  
Paula Thomé ◽  
Cristiane Kochi ◽  
Durval Damiani ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Aromatase Inhibitors ◽  
Adult Height ◽  
Final Height ◽  
Recombinant Human Growth Hormone ◽  
Human Growth ◽  
Bone Age ◽  
Height Loss ◽  
Retrospective Data Analysis ◽  
Height Gain

AbstractAromatase inhibitors (AIs) have been used to recover height loss due to their capacity to delay growth plate closure. Long-term studies describing final heights are needed to determine the efficacy and safety profiles of these drugs for the treatment of impaired growth. This study aims to identify the therapeutic efficiency of AIs in improve growth and to describe potential adverse effects during treatment. Retrospective data analysis of 96 adolescents, among which 22 patients already attained near-final height, were followed at outpatient clinics of two referral centers. Patients were all in puberty and present idiopathic decrease in predicted adult height. Patients were treated with Anastrozole (ANZ: 1 mg/day) or Letrozole (LTZ: 2.5 mg/day) with/without recombinant human growth hormone (0.05 mg/kg/day) for 1.0 to 3.5 years (2.1±1.2 years). Height gain, body mass index, lipid, liver enzyme, gonadotropins and testosterone levels were described before and at the end of treatment. Predicted adult height (PAH) and NF height were compared with the TH. The height SDS (adjusted to bone age) significantly increased (p<0.05) in all groups [0.8±0.7 (ANZ), 0.7±0.7 (ANZ+GH), 0.3±0.5 (LTZ), and 1.2±0.8 (LTZ+GH)]; the latter group exhibited the highest increment of PAH and growth recovery to the TH (p<0.004). No significant side effects were observed. AI treatment, especially when used in association with GH was able to improve growth and the attainment of familial target height.

scholarly journals Significance of Direct Confirmation of Growth Hormone Insensitivity for the Diagnosis of Primary IGF-I Deficiency

2020 ◽  
Vol 9 (1) ◽  
pp. 240
Author(s):  
Joanna Smyczyńska ◽  
Urszula Smyczyńska ◽  
Maciej Hilczer ◽  
Renata Stawerska ◽  
Andrzej Lewiński
Keyword(s):  
Growth Hormone ◽  
Final Height ◽  
Standard Deviation Score ◽  
Height Velocity ◽  
Gh Therapy ◽  
Significant Difference ◽  
Igf I ◽  
Growth Hormone Insensitivity ◽  
Stimulation Tests ◽  
Direct Confirmation

Primary insulin-like growth factor-I (IGF-I) deficiency is a synonym of growth hormone (GH) insensitivity (GHI), however the necessity of direct confirmation of GH resistance by IGF-I generation test (IGF-GT) is discussed. GHI may disturb intrauterine growth, nevertheless short children born small for gestational age (SGA) are treated with GH. We tested the hypothesis that children with appropriate birth size (AGA), height standard deviation score (SDS) <−3.0, GH peak in stimulation tests (stimGH) ≥10.0 µg/L, IGF-I <2.5 centile, and excluded GHI may benefit during GH therapy. The analysis comprised 21 AGA children compared with 6 SGA and 20 GH-deficient ones, with height SDS and IGF-I as in the studied group. All patients were treated with GH up to final height (FH). Height velocity, IGF-I, and IGF binding protein-3 (IGFBP-3) concentrations before and during first year of treatment were assessed. Effectiveness of therapy was better in GHD than in IGF-I deficiency (IGFD), with no significant difference between SGA and AGA groups. All but two AGA children responded well to GH. Pretreatment IGF-I and increase of height velocity (HV) during therapy but not the result of IGF-GT correlated with FH. As most AGA children with apparent severe IGFD benefit during GH therapy, direct confirmation of GHI seems necessary to diagnose true primary IGFD in them.

Growth Hormone Therapy in Children with Kabuki Syndrome: 1-year Treatment Results

2017 ◽  
Vol 88 (3-4) ◽  
pp. 258-264 ◽  
Author(s):  
Dina A. Schott ◽  
Willem J.M. Gerver ◽  
Constance T.R.M. Stumpel
Keyword(s):  
Growth Hormone ◽  
Gh Deficiency ◽  
Standard Deviation Score ◽  
Height Velocity ◽  
Kabuki Syndrome ◽  
Body Proportions ◽  
Leg Length ◽  
Gh Treatment ◽  
Igf I ◽  
Rhgh Treatment

Background/Aims: Kabuki syndrome (KS) is a rare genetic malformation syndrome, resulting in characteristic features such as short stature. We investigate whether growth hormone (GH) treatment increases linear height and influences body proportions in KS children. Methods: In this prospective study, 18 genetically confirmed prepubertal KS children (9 females and 9 males) aged from 3.8 to 10.1 years (mean 6.8 ± 2.1 years) were treated with recombinant human GH (rhGH) for 1 year. Calculations for height, height velocity, BMI, sitting height, and subischial leg length were made. Bone age, insulin-like growth factor (IGF-I), and IGF binding protein 3 (IGFBP-3) were also measured. Results: This study showed an increase in height standard deviation score (SDS) for the whole group from –2.40 to –1.69 (p < 0.05) after 1 year of rhGH treatment. The change in height SDS within 1 year was >0.7 SDS for 10 subjects and >0.5 SDS for 3 subjects. The mean IGF-I SDS at the start of the study was –0.70 (±1.07), which increased after 12 months to 1.41 (±0.91) (p < 0.05). KS children who received rhGH at a younger age displayed significantly greater increases in height than those who started when they were older. The same was true for both gene mutation KMT2D versus KDM6A and for GH deficiency versus non-GH deficiency KS children (p < 0.05). Throughout the course of rhGH treatment, the subjects’ body proportions remained normal. Conclusions: All participants experienced catch-up growth during the year of rhGH treatment, but without an influence on body proportions.

scholarly journals ACAN Gene Mutations in Short Children Born SGA and Response to Growth Hormone Treatment

2016 ◽  
Vol 102 (5) ◽  
pp. 1458-1467 ◽  
Author(s):  
Manouk van der Steen ◽  
Rolph Pfundt ◽  
Stephan J.W.H. Maas ◽  
Willie M. Bakker-van Waarde ◽  
Roelof J. Odink ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Gene Mutation ◽  
Gene Mutations ◽  
Bone Age ◽  
Hormone Treatment ◽  
Gh Treatment ◽  
Midface Hypoplasia ◽  
Short Children ◽  
Hormone Analog

Abstract Background: Some children born small for gestational age (SGA) show advanced bone age (BA) maturation during growth hormone (GH) treatment. ACAN gene mutations have been described in children with short stature and advanced BA. Objective: To determine the presence of ACAN gene mutations in short SGA children with advanced BA and assess the response to GH treatment. Methods: BA assessment in 290 GH-treated SGA children. ACAN sequencing in 29 children with advanced BA ≥0.5 years compared with calendar age. Results: Four of 29 SGA children with advanced BA had an ACAN gene mutation (13.8%). Mutations were related to additional characteristics: midface hypoplasia (P = 0.003), joint problems (P = 0.010), and broad great toes (P = 0.003). Children with one or fewer additional characteristic had no mutation. Of children with two additional characteristics, 50% had a mutation. Of children with three additional characteristics, 100% had a mutation. All GH-treated children with a mutation received gonadotropin-releasing hormone analog (GnRHa) treatment for 2 years from onset of puberty. At adult height, one girl was 5 cm taller than her mother and one boy was 8 cm taller than his father with the same ACAN gene mutation. Conclusion: This study expands the differential diagnosis of genetic variants in children born SGA and proposes a clinical scoring system for identifying subjects most likely to have an ACAN gene mutation. ACAN sequencing should be considered in children born SGA with persistent short stature, advanced BA, and midface hypoplasia, joint problems, or broad great toes. Our findings suggest that children with an ACAN gene mutation benefit from GH treatment with 2 years of GnRHa.

scholarly journals IGF-1 and Growth Response to Adult Height in a Randomized GH Treatment Trial in Short Non-GH-Deficient Children

2014 ◽  
Vol 99 (8) ◽  
pp. 2917-2924 ◽  
Author(s):  
Berit Kriström ◽  
Elena Lundberg ◽  
Björn Jonsson ◽  
Kerstin Albertsson-Wikland ◽  
Keyword(s):  
Clinical Trial ◽  
Growth Response ◽  
Adult Height ◽  
Bone Age ◽  
Controlled Clinical Trial ◽  
Dependent Manner ◽  
Gh Treatment ◽  
Randomized Controlled ◽  
Short Children ◽  
Height Gain

Context: GH treatment significantly increased adult height (AH) in a dose-dependent manner in short non-GH-deficient children in a randomized, controlled, clinical trial; the mean gain in height SD score (heightSDS) was 1.3 (range 0–3), compared with 0.2 in the untreated group. Objective: The objective of the study was to analyze the relationship between IGF-1SDS, IGF binding protein-3 SDS (IGFBP3SDS), and their ratioSDS with a gain in the heightSDS until AH in non-GH-deficient short children. Design and Setting: This was a randomized, controlled, multicenter clinical trial. Intervention: The intervention included GH treatment: 33 or 67 μg/kg · d plus untreated controls. Subjects: One hundred fifty-one non-GH-deficient short children were included in the intent-to-treat (ITT) population and 108 in the per-protocol (PP) population; 112 children in the ITT and 68 children in the PP populations had idiopathic short stature (ISS). Main Outcome Measures: Increments from baseline to on-treatment study mean IGF-1SDS (ΔIGF-1SDS), IGFBP3SDS, and IGF-1 to IGFBP3 ratioSDS were assessed in relationship to the gain in heightSDS. Results: Sixty-two percent of the variance in the gain in heightSDS in children on GH treatment could be explained by four variables: ΔIGF-1SDS (explaining 28%), bone age delay, birth length (the taller the better), and GH dose (the higher the better). The lower IGF-1SDS was at baseline, the higher was its increment during treatment. For both the AllPP- and the ISSPP-treated groups, the attained IGF-1SDS study level did not correlate with height gain. Conclusion: In short non-GH-deficient children, the GH dose-related increment in IGF-1SDS from baseline to mean study level was the most important explanatory variable for long-term growth response from the peripubertal period until AH, when IGF-1SDS, IGFBP3SDS, and their ratioSDS were compared concurrently.

scholarly journals Adult height after GH therapy in 188 Ullrich-Turner syndrome patients: results of the German IGLU Follow-up Study 2001

2002 ◽  
pp. 625-633 ◽  
Author(s):  
MB Ranke ◽  
CJ Partsch ◽  
A Lindberg ◽  
HG Dorr ◽  
M Bettendorf ◽  
...  
Keyword(s):  
Turner Syndrome ◽  
Adult Height ◽  
Bone Age ◽  
First Year ◽  
Gh Therapy ◽  
Gh Treatment ◽  
Height Gain ◽  
Puberty Onset

OBJECTIVES: We aimed to evaluate the factors influencing true adult height (HT) after long-term (from 1987 to 2000) GH treatment in Ullrich-Turner syndrome (UTS) based on modalities conceived in the 1980s. DESIGN: Out of 347 near-adult (>16 Years) patients from 96 German centres, whose longitudinal growth was documented within KIGS (Pharmacia International Growth Database), 188 (45, X=59%; bone age >15 Years) were available for further anthropometric measurements. RESULTS: At a median GH dose of 0.88 (10th/90th percentiles: 0.47/1.06) IU/kg per week, a gain of 6.0 (-1.3/+13) cm above the projected adult height was recorded. Variables were recorded at GH start, after 1 Year GH, puberty onset, and last visit on GH therapy. At these visits, the median ages were 11.7, 12.7, 14.2, 16.6 and 18.7 Years; and median heights, 0.4, 1.1, 1.7, 1.7 and 1.3 SDS (UTS) respectively. Height gain (DeltaHT) after GH discontinuation was 1.5 cm. Total DeltaHT correlated (P<0.001) negatively with bone age and HT SDS at GH start, but positively with DeltaHT after the first Year, DeltaHT at puberty onset, and GH duration. Final HT correlated (P<0.001) positively with HT at GH start, first-Year DeltaHT, and HT at puberty onset. Body mass index increased slightly (P<0.05), with values at start and adult follow-up correlating highly (R=0.70, P<0.001). No major side effects of GH occurred. CONCLUSIONS: GH dosages conceived in the 1980s are safe but too low for most UTS patients. HT gain and height are determined by age and HT at GH start. Height gain during the first Year on GH is indicative of overall height gain. After spontaneous or induced puberty, little gain in height occurs.

Sign in / Sign up

Export Citation Format

Share Document